Background: Certain heme proteins exhibit a pseudo-peroxidase activity that alters their function. Results: H 2 O 2 engages the peroxidase activity of indoleamine 2,3-dioxygenase (IDO) to oxidatively inactivate its dioxygenase activity, consume nitric oxide, and promote IDO protein nitration. Conclusion: IDO is a catalyst of physiological peroxidase reactions. Significance: IDO peroxidase activity has novel implications for the control and biological actions of this important immune regulatory enzyme.